The Stanford Mental Health Clinical Research Center (MHCRC) proposes to continue its productive operation in fostering multidisciplinary collaboration in the search for biological correlates of psychiatric illness. We will test pharmacological agents whose actions relate to specific biochemical hypothesis of psychopathology. In schizophrenia we examine cerebrospinal fluid (CSF) catecholamine, phenylethylamine, tyramine, and serotonin metabolites, and endorphin concentrations. We also measure platelet monoamine oxidase activity. We evaluate schizophrenic patients using neuropsychological testing asnd computerized axial tomographic scanning. Experimental treatments for schizophrenic patients include naloxone, Beta-endorphin, des-tyrosine-Gamma-endorphin and metkephamid (a methionine-enkephalin analogue). In depression we are measuring the same CSF neurotransmitter metabolites mentioned above, urinary MHPG, the pituitary thyrotropin response to thyrotropin-releasing hormone and the cortisol response to dexamethasone. We also assess schizophrenic and depressed patients and controls using a battery of event-related brain electrical potentials which reflect cortical excitability, stimulus intensity modulation and attention. We are investigating the utility of sleep variables such as sleep onset latency, REM latency, middle ear muscle activity, and burst eye movement activity among others, in distinguishing schizophrenic patients from depressed patients and from normal controls. In patients with manic psychosis, tardive dyskinesia, Huntington's chorea, Tourette syndrome, and dystonias, we are investigating neurotransmitter imbalance hypotheses by administering choinomimetics (physostigmine and choline chloride). Finally, we hope that the correlation of biochemical, psychological, physiological, and clinical variables will help classify patients with psychiatric disorders, predict their response to specific pharmacological treatments, and improve our understanding of the biological basis of psychopathology.